NCT02710370

Brief Summary

The purpose of this research study is to determine how gastric bypass surgery effects metabolism in obesity and Type 2 Diabetes. One mechanism that has been investigated in animal models is change to the biology of the small intestine (Roux limb) and how glucose and other fuels are metabolized (or how the body digests and uses sugar and other fuels). This study will evaluate the role of the intestine in the beneficial metabolic effects of gastric bypass surgery. It specifically will examine whether the intestine increases its metabolism and its activity, and whether this results in an increase in fuel utilization. Thirty two (32) subjects will be recruited (18 with and 14 without Type 2 Diabetes). At the time of gastric bypass surgery, a small piece of intestine that is usually discarded will be collected. At three time points over the first year after surgery, intestinal samples will be obtained by endoscopy or insertion of a lighted flexible tube through the mouth. Blood samples will be taken at all time points, as well. All samples will undergo comprehensive metabolic analyses. Comparisons will be made between the two groups to understand the metabolic changes over time and if there are differences between the two groups.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
46

participants targeted

Target at P25-P50 for all trials

Timeline
28mo left

Started Feb 2016

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress82%
Feb 2016Aug 2028

Study Start

First participant enrolled

February 1, 2016

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

February 5, 2016

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 16, 2016

Completed
12.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2028

Last Updated

July 11, 2025

Status Verified

July 1, 2025

Enrollment Period

12.6 years

First QC Date

February 5, 2016

Last Update Submit

July 8, 2025

Conditions

ObesityDiabetes Mellitus, Type 2Endocrine System DiseasesGlucose Metabolism DisordersMetabolic Diseases

Keywords

Bariatric SurgeryGastric BypassObesity/surgeryEndoscopy, Digestive SystemBlood Glucose/metabolismDiabetes Mellitus, Experimental/metabolismEnergy MetabolismGlucose/metabolismJejunum/metabolismMetabolomicsGene Expression

Outcome Measures

Primary Outcomes (15)

  • Description of intestinal morphology.

    Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.

    Baseline, at time of operation

  • Description of intestinal morphology.

    Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.

    1 month after surgery.

  • Description of intestinal morphology.

    Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.

    6 months after surgery.

  • Description of intestinal morphology.

    Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.

    12 months after surgery.

  • Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.

    Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).

    Baseline, at time of operation.

  • Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.

    Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).

    1 month after surgery.

  • Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.

    Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).

    6 months after surgery.

  • Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.

    Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).

    12 months after surgery.

  • Description of metabolite profile of the intestine and serum/plasma.

    Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.

    Baseline, at time of operation.

  • Description of metabolite profile of the intestine and serum/plasma.

    Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.

    1 month after surgery.

  • Description of metabolite profile of the intestine and serum/plasma.

    Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.

    6 months after surgery.

  • Description of metabolite profile of the intestine and serum/plasma.

    Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.

    12 months after surgery.

  • Change from baseline (time of operation) in morphological signatures.

    Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.

  • Change from baseline (time of operation) in gene and protein expression for markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.

    Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.

  • Change from baseline (time of operation) in metabolite profile.

    Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.

Secondary Outcomes (13)

  • Comparison of intestinal morphology signature between patients with and without diabetes.

    Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.

  • Comparison of gene and protein expression profiles and levels of expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways between patients with and without diabetes.

    Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.

  • Comparison of metabolite profile between patients with and without diabetes.

    Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.

  • Correlation of intestinal morphology signature with eating behaviors. Assessed by specific questionnaire.

    Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.

  • Correlation of eating behaviors with gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways. Assessed by specific questionnaire.

    Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.

  • +8 more secondary outcomes

Study Arms (2)

Controls

Patients who meet criteria for gastric bypass surgery, and do not have a documented history of Type 1 or Type 2 Diabetes.

Participants with Type 2 Diabetes

Patients who meet criteria for gastric bypass surgery, and have a documented history of Type 2 Diabetes.

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients who plan to undergo gastric bypass, with or without Type 2 Diabetes.

You may qualify if:

  • Patients who elect to undergo gastric bypass surgery
  • Standard bariatric surgery criteria (A BMI 35 to 40 kg/m2, with an obesity comorbid condition, OR BMI 40 kg/m2 or \>).

You may not qualify if:

  • Prior bariatric or foregut surgery
  • Documented history of Type 1 Diabetes
  • Poor overall general health
  • Impaired mental status
  • Drug and/or alcohol addiction
  • Currently smoking
  • Pregnant or plans to become pregnant
  • Portal hypertension and/or cirrhosis

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (9)

  • Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science. 2013 Jul 26;341(6144):406-10. doi: 10.1126/science.1235103.

    PMID: 23888041BACKGROUND

  • Laferrere B. Do we really know why diabetes remits after gastric bypass surgery? Endocrine. 2011 Oct;40(2):162-7. doi: 10.1007/s12020-011-9514-x. Epub 2011 Aug 19.

    PMID: 21853297BACKGROUND

  • Courcoulas AP, Christian NJ, Belle SH, Berk PD, Flum DR, Garcia L, Horlick M, Kalarchian MA, King WC, Mitchell JE, Patterson EJ, Pender JR, Pomp A, Pories WJ, Thirlby RC, Yanovski SZ, Wolfe BM; Longitudinal Assessment of Bariatric Surgery (LABS) Consortium. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA. 2013 Dec 11;310(22):2416-25. doi: 10.1001/jama.2013.280928.

    PMID: 24189773BACKGROUND

  • Stylopoulos N, Hoppin AG, Kaplan LM. Roux-en-Y gastric bypass enhances energy expenditure and extends lifespan in diet-induced obese rats. Obesity (Silver Spring). 2009 Oct;17(10):1839-47. doi: 10.1038/oby.2009.207. Epub 2009 Jun 25.

    PMID: 19556976BACKGROUND

  • Arterburn DE, Courcoulas AP. Bariatric surgery for obesity and metabolic conditions in adults. BMJ. 2014 Aug 27;349:g3961. doi: 10.1136/bmj.g3961.

    PMID: 25164369BACKGROUND

  • Nestoridi E, Kvas S, Kucharczyk J, Stylopoulos N. Resting energy expenditure and energetic cost of feeding are augmented after Roux-en-Y gastric bypass in obese mice. Endocrinology. 2012 May;153(5):2234-44. doi: 10.1210/en.2011-2041. Epub 2012 Mar 13.

    PMID: 22416083BACKGROUND

  • Stefater-Richards MA, Panciotti C, Feldman HA, Gourash WF, Shirley E, Hutchinson JN, Golick L, Park SW, Courcoulas AP, Stylopoulos N. Gut adaptation after gastric bypass in humans reveals metabolically significant shift in fuel metabolism. Obesity (Silver Spring). 2023 Jan;31(1):49-61. doi: 10.1002/oby.23585.

    PMID: 36541157BACKGROUND

  • Stefater-Richards MA, Panciotti C, Esteva V, Lerner M, Petty CR, Gourash WF, Courcoulas AP. Gastric bypass elicits persistent gut adaptation and unique diabetes remission-related metabolic gene regulation. Obesity (Silver Spring). 2024 Nov;32(11):2135-2148. doi: 10.1002/oby.24135. Epub 2024 Oct 15.

    PMID: 39410706BACKGROUND

  • Courcoulas AP, Stefater MA, Shirley E, Gourash WF, Stylopoulos N. The Feasibility of Examining the Effects of Gastric Bypass Surgery on Intestinal Metabolism: Prospective, Longitudinal Mechanistic Clinical Trial. JMIR Res Protoc. 2019 Jan 24;8(1):e12459. doi: 10.2196/12459.

    PMID: 30679147BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Intestinal samples, serum and plasma will be collected from patients who have had gastric bypass surgery. Tissue samples will be processed for histo-morphological examination and for RNA, protein and metabolomics analyses.

MeSH Terms

Conditions

ObesityDiabetes Mellitus, Type 2Endocrine System DiseasesGlucose Metabolism DisordersMetabolic DiseasesDiabetes Mellitus

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Anita Courcoulas, MD, MPH

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Minimally Invasive Bariatric & General Surgery

Study Record Dates

First Submitted

February 5, 2016

First Posted

March 16, 2016

Study Start

February 1, 2016

Primary Completion (Estimated)

August 31, 2028

Study Completion (Estimated)

August 31, 2028

Last Updated

July 11, 2025

Record last verified: 2025-07

Locations

US(1)